Expeditious synthesis of the fused hexacycle of puberuline C via a radical-based cyclization/translocation/cyclization process?

Chemical Science Pub Date: 2016-03-18 DOI: 10.1039/C6SC00671J

Abstract

The fused 6/7/5/6/6/6-hexacyclic ring system of puberuline C was assembled in 18 steps from 2-(ethoxycarbonyl)cyclohexanone. After the azabicyclo[3.3.1]nonane derivative was sequentially coupled with propargyl magnesium bromide, 2-iodo cyclopentenone and allyl bromide, the pentacycle was constructed in a single step via a radical-based cyclization/translocation/cyclization process. The C11-bridgehead radical generated via C–Br homolysis participated in a 7-endo cyclization, and the 1,5-hydrogen translocation of the resultant radical was followed by transannular 6-exo cyclization to simultaneously realize the construction of the two rings and the introduction of the five contiguous stereocenters. The last 6-exo cyclization was induced by the Mukaiyama aldol reaction, and the C16–ketone was stereoselectively reduced by the action of SmI2/t-BuOH, leading for the first time to the synthesis of the entire hexacycle of puberuline C.

Graphical abstract: Expeditious synthesis of the fused hexacycle of puberuline C via a radical-based cyclization/translocation/cyclization process
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